Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Elucidating the underlying mechanisms of this disease could provide new therapeutic strategies for treating HCC. Here, we identified a novel role of DEAD-box helicase 24 (DDX24), a member of the DEAD-box protein family, in promoting HCC progression. DDX24 levels were significantly elevated in HCC tissues and were associated with poor prognosis of HCC. Overexpression of DDX24 promoted HCC migration and proliferation in vitro and in vivo, whereas suppression of DDX24 inhibited both functions. Mechanistically, DDX24 bound the mRNA618-624nt of laminin subunit beta 1 (LAMB1) and increased its stability in a manner dependent upon the interaction between nucleolin (NCL) and the C-terminal region of DDX24. Moreover, RFX8 was identified as a DDX24 promoter-binding protein that transcriptionally upregulated DDX24 expression. Collectively, these findings demonstrate that the RFX8/DDX24/LAMB1 axis promotes HCC progression, providing potential therapeutic targets for HCC.
Background The prevention of peripherally inserted central catheters (PICC)-associated BSI and central venous catheters (CVC)-associated BSI have been a topic of national importance in China. Therefore, we aimed to explore the epidemiological characteristics of central line-associated bloodstream infection (CLABSI), and to evaluate whether PICCs were associated with a protective effect for CLABSI. Methods A retrospective cohort study was conducted in teaching hospital in Western China. All adult patients received a CVC or PICC during their hospital stay were included from January 2017 to December 2020. Primary endpoint was CLABSI up to 30 days after CVC or PICC placement. Propensity scores with a 2:1 match was used to account for potential confounders, and restricted cubic spline was used to visualize the risk of CLABSI at different time points during the catheterization. Results A total of 224687 devices (180522 PICCs and 45965 CVCs) in 24879 patients were included. The overall incidence was 1.8 CLABSIs per 1000 catheter-days. The odds ratio (OR) value increased day by day after PICC insertion, reached a relatively high point on the 4th day, and decreased from days 5 through 8. From the 9th day of intubation the OR value began to gradually increase day by day again. After covariate adjustment using propensity scores, CVCs were associated with higher risk of CLABSI (adjHR = 3.27, 95% CI 2.38–4.49) compared with PICCs. Conclusions PICCs have a protective role and the effect of fluctuation curve feature in CLABSI when compared to CVCs, and the first 8 calendar days after CVC insertion are the acute stage of CVC-associated BSI.
Human telomerase reverse transcriptase (hTERT) is highly expressed in many tumors and is essential for tumorigenesis and metastasis in multiple cancers. However, the molecular mechanisms underlying its high expression level in hepatocellular carcinoma (HCC) remain unclear. In this study, we identified X-ray repair cross-complementing 5 (XRCC5), a novel hTERT promoter-binding protein in HCC cells, using biotin-streptavidin-agarose pull-down assay. We found that XRCC5 was highly expressed in HCC cells, in which it transcriptionally upregulated hTERT. Functionally, the transgenic expression of XRCC5 promoted HCC progression and 5-fluorouracil resistance, whereas short hairpin RNA knockdown of XRCC5 had converse effects in vitro and in vivo. Moreover, hTERT overexpression reversed XRCC5 knockdown-or 5-fluorouracil (5-Fu)-mediated HCC inhibition. Mechanistically, nuclear-factor-erythroid-2-related factor 2 (NRF2) interacted with XRCC5, which in turn upregulated hTERT. However, the upregulation was insignificant when NRF2 was reduced, suggesting that the XRCC5-mediated hTERT expression was NRF2 dependent. The HCC patients with high expression levels of XRCC5 and hTERT had shorter overall survival times compared with those with low XRCC5 and hTERT levels in their tumor tissues. Collectively, our study demonstrates the molecular mechanisms of the XRCC5/NRF2/hTERT signaling in HCC metastasis, which will aid in the identification of novel strategies for the diagnosis and treatment of HCC.
Purpose: Non-small cell lung cancer (NSCLC) is a leading cause of cancer death, and metastasis is a crucial determinant of increased cancer mortality. DDX24 has garnered increased attention due to its correlation with tumorigenesis and malignant progression. However, the correlation between DDX24 and NSCLC remains unclear.Methods: DDX24 expression in NSCLC tissues and survival rate of patients was analyzed using bioinformatic analysis. Transwell assays, wound-healing assays, and tail vein lung colonization models were employed to determine the role of DDX24 in migration and invasion in vitro and in vivo. We searched for DDX24interacting proteins using co-immunoprecipitation followed by mass spectroscopy and verified the interaction. The influence of DDX24 on RPL5 expression and ubiquitination was examined using protein stability assays.Results: DDX24 expression was upregulated in NSCLC cell lines and tumors of patients, particularly those with high tumor grades. A high DDX24 level was also correlated with a poor prognosis. DDX24 upregulation enhanced the migration and invasion ability of NSCLC cells, whereas its downregulation had the opposite effects. In vivo xenograft experiments confirmed that tumors with high DDX24
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